PPP1R15A: Difference between revisions

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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Protein phosphatase 1 regulatory subunit 15A''' also known as '''growth arrest and DNA damage-inducible protein GADD34''' is a [[protein]] that in humans is encoded by the ''PPP1R15A'' [[gene]].<ref name="pmid9153226">{{cite journal | vauthors = Hollander MC, Zhan Q, Bae I, ((Fornace AJ Jr)) | title = Mammalian GADD34, an apoptosis- and DNA damage-inducible gene | journal = J Biol Chem | volume = 272 | issue = 21 | pages = 13731–7 |date=Jul 1997 | pmid = 9153226 | pmc =  | doi =10.1074/jbc.272.21.13731  }}</ref><ref name="pmid9413226">{{cite journal | vauthors = Korabiowska M, Betke H, Kellner S, Stachura J, Schauer A | title = Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas | journal = Anticancer Res | volume = 17 | issue = 5A | pages = 3697–700 |date=Jan 1998 | pmid = 9413226 | pmc = | doi = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23645| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
The Gadd34/MyD116 gene was originally discovered as a member in a set of gadd and MyD mammalian genes encoding acidic proteins that synergistically suppress cell growth.<ref name="pmid8139541">{{cite journal | vauthors = Zhan Q, Lord KA, Alamo I, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ | title = The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth | journal = Mol. Cell. Biol. | volume = 14 | issue = 4 | pages = 2361–71 |date=April 1994 | pmid = 8139541 | pmc = 358603 | doi = 10.1128/mcb.14.4.2361}}</ref> Later on it has been characterized as a gene playing a role in [[endoplasmic reticulum|ER]] stress-induced cell death, being a target of [[ATF4]] that plays a role in ER-mediated cell death via promoting protein [[dephosphorylation]] of [[eIF2]]α and reversing translational inhibition.<ref name="pmid23850759">{{cite journal | vauthors = Sano R, Reed JC | title = ER stress-induced cell death mechanisms | journal = Biochim. Biophys. Acta | volume = 1833| issue = 12| pages = 3460–70|date=July 2013 | pmid = 23850759 | doi = 10.1016/j.bbamcr.2013.06.028 | pmc=3834229}}</ref>
{{GNF_Protein_box
| image =
| image_source = 
| PDB =
| Name = Protein phosphatase 1, regulatory (inhibitor) subunit 15A
| HGNCid = 14375
| Symbol = PPP1R15A
| AltSymbols =; GADD34
| OMIM = 
| ECnumber = 
| Homologene = 8639
| MGIid = 1100516
| GeneAtlas_image1 = PBB_GE_PPP1R15A_37028_at_tn.png
| GeneAtlas_image2 = PBB_GE_PPP1R15A_202014_at_tn.png
| Function =  
| Component =  
| Process = {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0006974 |text = response to DNA damage stimulus}} {{GNF_GO|id=GO:0007050 |text = cell cycle arrest}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 23645
    | Hs_Ensembl = ENSG00000087074
    | Hs_RefseqProtein = NP_055145
    | Hs_RefseqmRNA = NM_014330
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 54067490
    | Hs_GenLoc_end = 54071126
    | Hs_Uniprot =
    | Mm_EntrezGene = 17872
    | Mm_Ensembl = ENSMUSG00000040435
    | Mm_RefseqmRNA = NM_008654
    | Mm_RefseqProtein = NP_032680
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 45390962
    | Mm_GenLoc_end = 45394255
    | Mm_Uniprot = Q3U3L5
  }}
}}
'''Protein phosphatase 1, regulatory (inhibitor) subunit 15A''', also known as '''PPP1R15A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23645| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
 
| section_title =
This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of [[p53]] status, and its protein response is correlated with apoptosis following ionizing radiation.<ref name="entrez"/>
| summary_text = This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation.<ref name="entrez">{{cite web | title = Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23645| accessdate = }}</ref>
 
}}
==Interactions==
PPP1R15A has been shown to [[Protein-protein interaction|interact]] with:
* [[BAG1]]<ref name = pmid12724406/>
* [[LYN]],<ref name = pmid11517336>{{cite journal | vauthors = Grishin AV, Azhipa O, Semenov I, Corey SJ | title = Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 18 | pages = 10172–7 | year = 2001 | pmid = 11517336 | pmc = 56934 | doi = 10.1073/pnas.191130798 }}</ref>
* [[MLL (gene)|MLL]],<ref name = pmid10490642/>
* [[PPP1CA]],<ref name = pmid12724406>{{cite journal | vauthors = Hung WJ, Roberson RS, Taft J, Wu DY | title = Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions | journal = Mol. Cell. Biol. | volume = 23 | issue = 10 | pages = 3477–86 | year = 2003 | pmid = 12724406 | pmc = 164759 | doi = 10.1128/MCB.23.10.3477-3486.2003}}</ref><ref name = pmid12016208/><ref name = pmid11564868/>
* [[PPP1CB]],<ref name = pmid12016208>{{cite journal | vauthors = Wu DY, Tkachuck DC, Roberson RS, Schubach WH | title = The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity | journal = J. Biol. Chem. | volume = 277 | issue = 31 | pages = 27706–15 | year = 2002 | pmid = 12016208 | doi = 10.1074/jbc.M200955200 }}</ref><ref name = pmid11564868>{{cite journal | vauthors = Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S | title = Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1 | journal = Mol. Cell. Biol. | volume = 21 | issue = 20 | pages = 6841–50 | year = 2001 | pmid = 11564868 | pmc = 99861 | doi = 10.1128/MCB.21.20.6841-6850.2001 }}</ref>
* [[PPP1CC]],<ref name = pmid12016208/><ref name = pmid11564868/>
* [[SMARCB1]],<ref name = pmid10490642>{{cite journal | vauthors = Adler HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ, Tkachuk DC | title = Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins | journal = Mol. Cell. Biol. | volume = 19 | issue = 10 | pages = 7050–60 | year = 1999 | pmid = 10490642 | pmc = 84700 | doi = 10.1128/mcb.19.10.7050}}</ref><ref name = pmid12016208/> and
* [[TSN (gene)|TSN]].<ref name = pmid10434033>{{cite journal | vauthors = Hasegawa T, Isobe K | title = Evidence for the interaction between Translin and GADD34 in mammalian cells | journal = Biochim. Biophys. Acta | volume = 1428 | issue = 2–3 | pages = 161–8 | year = 1999 | pmid = 10434033 | doi = 10.1016/s0304-4165(99)00060-4}}</ref>


==References==
==References==
{{reflist|2}}
{{Reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  | vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
| citations =
*{{cite journal   |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
*{{cite journal  | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
*{{cite journal  | vauthors=Hasegawa T, Isobe K |title=Evidence for the interaction between Translin and GADD34 in mammalian cells. |journal=Biochim. Biophys. Acta |volume=1428 |issue= 2–3 |pages= 161–8 |year= 1999 |pmid= 10434033 |doi=  10.1016/s0304-4165(99)00060-4}}
*{{cite journal | author=Hollander MC, Zhan Q, Bae I, Fornace AJ |title=Mammalian GADD34, an apoptosis- and DNA damage-inducible gene. |journal=J. Biol. Chem. |volume=272 |issue= 21 |pages= 13731-7 |year= 1997 |pmid= 9153226 |doi=  }}
*{{cite journal   |vauthors=Adler HT, Chinery R, Wu DY, etal |title=Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins. |journal=Mol. Cell. Biol. |volume=19 |issue= 10 |pages= 7050–60 |year= 2000 |pmid= 10490642 |doi=  10.1128/mcb.19.10.7050| pmc=84700  }}
*{{cite journal  | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi=  }}
*{{cite journal  | vauthors=Hasegawa T, Yagi A, Isobe K |title=Interaction between GADD34 and kinesin superfamily, KIF3A. |journal=Biochem. Biophys. Res. Commun. |volume=267 |issue= 2 |pages= 593–6 |year= 2000 |pmid= 10631107 |doi= 10.1006/bbrc.1999.1991 }}
*{{cite journal | author=Korabiowska M, Betke H, Kellner S, ''et al.'' |title=Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas. |journal=Anticancer Res. |volume=17 |issue= 5A |pages= 3697-700 |year= 1998 |pmid= 9413226 |doi=  }}
*{{cite journal  | vauthors=Hasegawa T, Xiao H, Hamajima F, Isobe K |title=Interaction between DNA-damage protein GADD34 and a new member of the Hsp40 family of heat shock proteins that is induced by a DNA-damaging reagent. |journal=Biochem. J. |volume=352 |issue= 3|pages= 795–800 |year= 2001 |pmid= 11104688 |doi= 10.1042/0264-6021:3520795| pmc=1221519 }}
*{{cite journal  | author=Hasegawa T, Isobe K |title=Evidence for the interaction between Translin and GADD34 in mammalian cells. |journal=Biochim. Biophys. Acta |volume=1428 |issue= 2-3 |pages= 161-8 |year= 1999 |pmid= 10434033 |doi= }}
*{{cite journal  | vauthors=Grishin AV, Azhipa O, Semenov I, Corey SJ |title=Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 18 |pages= 10172–7 |year= 2001 |pmid= 11517336 |doi= 10.1073/pnas.191130798  | pmc=56934 }}
*{{cite journal  | author=Adler HT, Chinery R, Wu DY, ''et al.'' |title=Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins. |journal=Mol. Cell. Biol. |volume=19 |issue= 10 |pages= 7050-60 |year= 2000 |pmid= 10490642 |doi=  }}
*{{cite journal   |vauthors=Connor JH, Weiser DC, Li S, etal |title=Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. |journal=Mol. Cell. Biol. |volume=21 |issue= 20 |pages= 6841–50 |year= 2001 |pmid= 11564868 |doi= 10.1128/MCB.21.20.6841-6850.2001  | pmc=99861 }}
*{{cite journal  | author=Hasegawa T, Yagi A, Isobe K |title=Interaction between GADD34 and kinesin superfamily, KIF3A. |journal=Biochem. Biophys. Res. Commun. |volume=267 |issue= 2 |pages= 593-6 |year= 2000 |pmid= 10631107 |doi= 10.1006/bbrc.1999.1991 }}
*{{cite journal  | vauthors=Wu DY, Tkachuck DC, Roberson RS, Schubach WH |title=The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity. |journal=J. Biol. Chem. |volume=277 |issue= 31 |pages= 27706–15 |year= 2002 |pmid= 12016208 |doi= 10.1074/jbc.M200955200 }}
*{{cite journal | author=Hasegawa T, Xiao H, Hamajima F, Isobe K |title=Interaction between DNA-damage protein GADD34 and a new member of the Hsp40 family of heat shock proteins that is induced by a DNA-damaging reagent. |journal=Biochem. J. |volume=352 Pt 3 |issue= |pages= 795-800 |year= 2001 |pmid= 11104688 |doi= }}
*{{cite journal  | vauthors=Korabiowska M, Cordon-Cardo C, Betke H  | author2-link=Carlos Cordon-Cardo  |title=GADD153 is an independent prognostic factor in melanoma: immunohistochemical and molecular genetic analysis. |journal=Histol. Histopathol. |volume=17 |issue= 3 |pages= 805–11 |year= 2003 |pmid= 12168790 |doi= |display-authors=etal}}
*{{cite journal  | author=Grishin AV, Azhipa O, Semenov I, Corey SJ |title=Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 18 |pages= 10172-7 |year= 2001 |pmid= 11517336 |doi= 10.1073/pnas.191130798 }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
*{{cite journal  | author=Connor JH, Weiser DC, Li S, ''et al.'' |title=Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. |journal=Mol. Cell. Biol. |volume=21 |issue= 20 |pages= 6841-50 |year= 2001 |pmid= 11564868 |doi= 10.1128/MCB.21.20.6841-6850.2001 }}
*{{cite journal  | vauthors=Brush MH, Weiser DC, Shenolikar S |title=Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. |journal=Mol. Cell. Biol. |volume=23 |issue= 4 |pages= 1292–303 |year= 2003 |pmid= 12556489 |doi=10.1128/MCB.23.4.1292-1303.2003  | pmc=141149 }}
*{{cite journal | author=Wu DY, Tkachuck DC, Roberson RS, Schubach WH |title=The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity. |journal=J. Biol. Chem. |volume=277 |issue= 31 |pages= 27706-15 |year= 2002 |pmid= 12016208 |doi= 10.1074/jbc.M200955200 }}
*{{cite journal  | vauthors=Hung WJ, Roberson RS, Taft J, Wu DY |title=Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions. |journal=Mol. Cell. Biol. |volume=23 |issue= 10 |pages= 3477–86 |year= 2003 |pmid= 12724406 |doi=10.1128/MCB.23.10.3477-3486.2003  | pmc=164759  }}
*{{cite journal  | author=Korabiowska M, Cordon-Cardo C, Betke H, ''et al.'' |title=GADD153 is an independent prognostic factor in melanoma: immunohistochemical and molecular genetic analysis. |journal=Histol. Histopathol. |volume=17 |issue= 3 |pages= 805-11 |year= 2003 |pmid= 12168790 |doi=  }}
*{{cite journal  | vauthors=Hollander MC, Poola-Kella S, Fornace AJ |title=Gadd34 functional domains involved in growth suppression and apoptosis. |journal=Oncogene |volume=22 |issue= 25 |pages= 3827–32 |year= 2003 |pmid= 12813455 |doi= 10.1038/sj.onc.1206567 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | vauthors=Powolny A, Takahashi K, Hopkins RG, Loo G |title=Induction of GADD gene expression by phenethylisothiocyanate in human colon adenocarcinoma cells. |journal=J. Cell. Biochem. |volume=90 |issue= 6 |pages= 1128–39 |year= 2004 |pmid= 14635187 |doi= 10.1002/jcb.10733 }}
*{{cite journal  | author=Brush MH, Weiser DC, Shenolikar S |title=Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. |journal=Mol. Cell. Biol. |volume=23 |issue= 4 |pages= 1292-303 |year= 2003 |pmid= 12556489 |doi= }}
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Hung WJ, Roberson RS, Taft J, Wu DY |title=Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions. |journal=Mol. Cell. Biol. |volume=23 |issue= 10 |pages= 3477-86 |year= 2003 |pmid= 12724406 |doi= }}
*{{cite journal   |vauthors=Shi W, Sun C, He B, etal |title=GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. |journal=J. Cell Biol. |volume=164 |issue= 2 |pages= 291–300 |year= 2004 |pmid= 14718519 |doi= 10.1083/jcb.200307151  | pmc=2172339 }}
*{{cite journal | author=Hollander MC, Poola-Kella S, Fornace AJ |title=Gadd34 functional domains involved in growth suppression and apoptosis. |journal=Oncogene |volume=22 |issue= 25 |pages= 3827-32 |year= 2003 |pmid= 12813455 |doi= 10.1038/sj.onc.1206567 }}
*{{cite journal   |vauthors=Colland F, Jacq X, Trouplin V, etal |title=Functional proteomics mapping of a human signaling pathway. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324–32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 | pmc=442148 }}
*{{cite journal | author=Powolny A, Takahashi K, Hopkins RG, Loo G |title=Induction of GADD gene expression by phenethylisothiocyanate in human colon adenocarcinoma cells. |journal=J. Cell. Biochem. |volume=90 |issue= 6 |pages= 1128-39 |year= 2004 |pmid= 14635187 |doi= 10.1002/jcb.10733 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal | author=Shi W, Sun C, He B, ''et al.'' |title=GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. |journal=J. Cell Biol. |volume=164 |issue= 2 |pages= 291-300 |year= 2004 |pmid= 14718519 |doi= 10.1083/jcb.200307151 }}
*{{cite journal  | author=Colland F, Jacq X, Trouplin V, ''et al.'' |title=Functional proteomics mapping of a human signaling pathway. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1324-32 |year= 2004 |pmid= 15231748 |doi= 10.1101/gr.2334104 }}
}}
{{refend}}
{{refend}}
{{gene-19-stub}}
{{WikiDoc Sources}}

Latest revision as of 18:33, 7 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Protein phosphatase 1 regulatory subunit 15A also known as growth arrest and DNA damage-inducible protein GADD34 is a protein that in humans is encoded by the PPP1R15A gene.[1][2][3]

The Gadd34/MyD116 gene was originally discovered as a member in a set of gadd and MyD mammalian genes encoding acidic proteins that synergistically suppress cell growth.[4] Later on it has been characterized as a gene playing a role in ER stress-induced cell death, being a target of ATF4 that plays a role in ER-mediated cell death via promoting protein dephosphorylation of eIF2α and reversing translational inhibition.[5]

Function

This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The induction of this gene by ionizing radiation occurs in certain cell lines regardless of p53 status, and its protein response is correlated with apoptosis following ionizing radiation.[3]

Interactions

PPP1R15A has been shown to interact with:

References

  1. ↑ Hollander MC, Zhan Q, Bae I, Fornace AJ Jr (Jul 1997). "Mammalian GADD34, an apoptosis- and DNA damage-inducible gene". J Biol Chem. 272 (21): 13731–7. doi:10.1074/jbc.272.21.13731. PMID 9153226.
  2. ↑ Korabiowska M, Betke H, Kellner S, Stachura J, Schauer A (Jan 1998). "Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas". Anticancer Res. 17 (5A): 3697–700. PMID 9413226.
  3. ↑ 3.0 3.1 "Entrez Gene: PPP1R15A protein phosphatase 1, regulatory (inhibitor) subunit 15A".
  4. ↑ Zhan Q, Lord KA, Alamo I, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace AJ (April 1994). "The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth". Mol. Cell. Biol. 14 (4): 2361–71. doi:10.1128/mcb.14.4.2361. PMC 358603. PMID 8139541.
  5. ↑ Sano R, Reed JC (July 2013). "ER stress-induced cell death mechanisms". Biochim. Biophys. Acta. 1833 (12): 3460–70. doi:10.1016/j.bbamcr.2013.06.028. PMC 3834229. PMID 23850759.
  6. ↑ 6.0 6.1 Hung WJ, Roberson RS, Taft J, Wu DY (2003). "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions". Mol. Cell. Biol. 23 (10): 3477–86. doi:10.1128/MCB.23.10.3477-3486.2003. PMC 164759. PMID 12724406.
  7. ↑ Grishin AV, Azhipa O, Semenov I, Corey SJ (2001). "Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10172–7. doi:10.1073/pnas.191130798. PMC 56934. PMID 11517336.
  8. ↑ 8.0 8.1 Adler HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ, Tkachuk DC (1999). "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins". Mol. Cell. Biol. 19 (10): 7050–60. doi:10.1128/mcb.19.10.7050. PMC 84700. PMID 10490642.
  9. ↑ 9.0 9.1 9.2 9.3 Wu DY, Tkachuck DC, Roberson RS, Schubach WH (2002). "The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity". J. Biol. Chem. 277 (31): 27706–15. doi:10.1074/jbc.M200955200. PMID 12016208.
  10. ↑ 10.0 10.1 10.2 Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S (2001). "Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1". Mol. Cell. Biol. 21 (20): 6841–50. doi:10.1128/MCB.21.20.6841-6850.2001. PMC 99861. PMID 11564868.
  11. ↑ Hasegawa T, Isobe K (1999). "Evidence for the interaction between Translin and GADD34 in mammalian cells". Biochim. Biophys. Acta. 1428 (2–3): 161–8. doi:10.1016/s0304-4165(99)00060-4. PMID 10434033.

Further reading

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